The broad objectives of these proposed studies are (1) to investigate the system which metabolizes volatile anesthetics in humans and to determine the similarities or differences compared to the rat and (2) to explore the possibility that intermediates produced in the course of this metabolism can lead to toxic side effects if in large enough concentration. The enzyme systems which catalyze the biotransformations of the volatile anesthetics will be studied, in vitro, in liver samples from rat and humans. Other studies will be carried out to identify the metabolic products of these biotransformations and to determine if there are species differences in these pathways. These samples of human and rats liver will be apparently normal in all respects and free of anesthetics or other drugs at the time of use. Additional studies will be performed to determine the mechanisms of biotransformation. A better understanding of the biotransformations of volatile anesthetic agents could be very important in explaining some of the unexpected and sometimes lethal reactions observed in clinical anesthesia. BIBLIOGRAPHIC REFERENCES: Tinker, J. H., Gandolfi, A. J. and Van Dyke, R. A.: Elevation of Plasma Bromide Levels in Patients Following Halothane Anesthesia: Time Correlation with Total Halothane Dosage. Anesthesiology. 44:194-196 (March) 1976. Widger, L. A., Gandolfi, A. J. and Van Dyke, R. A.: Hypoxic and Halothane Metabolism In Vivo Release of Inorganic Fluoride and Halothane Metabolite Binding to Cellular Constituents. Anesthesiology. 44:197-201 (March) 1976.